Project Summary A small minority of the 25 million US smokers who receive primary care each year receive evidence-based smoking treatment. Healthcare systems have enormous potential to connect smokers with high quality, evidence-based care. Diverse strategies have been used to increase treatment use, but treatment reach remains stubbornly low. The proposed research study will be the first rigorous factorial experiment to optimize a package of centralized healthcare system interventions to enhance smoking cessation treatment reach, and through this mediating pathway, reduce smoking prevalence after 2 years of reach intervention exposure and treatment access. Intervention components with promising empirical support and grounding in behavioral theory will be fully crossed in a 2x2x2x2 factorial experiment in 1664 patients who smoke daily from 8 primary care clinics. These patient-focused intervention components include: 1) monetary incentives for treatment initiation, 2) electronic-health-record (EHR)-enabled automation of quarterly tailored treatment invitations offering low-barrier treatment access, and 3) proactive telephone care management and motivational intervention. These components will be used to promote use of either standard care (referral to a toll-free tobacco quitline and the primary care provider), or to more intensive treatment (3 phone counseling sessions with either combination nicotine replacement therapy or varenicline), as randomly assigned on a 4th experimental factor (access to intensive treatment). All 4 experimental intervention components will be on or off (as randomly assigned) for 2 years to permit analysis of their cumulative impact on treatment reach and abstinence among primary care patients who are not initially willing to make a quit attempt. Analyses after 1 year of follow up will identify an especially effective (optimized) reach-intervention package to be evaluated in the Optimized Care Project in this Program Project. Clinic-based recruitment will support the project aims to identify: 1) a highly effective intervention package that promotes usual and intensive treatment use (reach) and downstream abstinence from smoking at low cost, 2) the mediating pathways for these effects, and 3) subpopulations of patients who particularly benefit from these intervention components (reach representativeness). This pragmatic project will use diverse real-world clinics, clinic staff interventionists, and patient participants, with minimal assessment to enhance generalizability and dissemination potential (as per RE-AIM). At the same time, rigorous experimental design and statistical analyses will enhance internal validity. This project will uniquely optimize interventions to enhance smoking cessation treatment reach. The project will be integrated into the Program Project to yield additional information (e.g., whether some components are more difficult to implement than others; how an optimized reach intervention works with optimized cessation treatments). The project will identify interventions that may prevent cancer and other chronic illnesses by connecting more smokers with effective smoking cessation treatments.